P. Singh1, P. Patel2, S. Fernandez2, P. Volden2, A. Spratt3, N. Jaskowiak1, M. Brady2, S. Conzen2, J. Park1 1University Of Chicago,Department Of Surgery,Chicago, IL, USA 2University Of Chicago,Department Of Medicine,Chicago, IL, USA 3University Of Chicago,The Division Of Biological Sciences,Chicago, IL, USA
Introduction: The use of lower abdominal tissue for breast cancer reconstruction is a mainstay for reconstructive surgeons. Free flap (e.g. deep inferior epigastric perforator flap) reconstruction involves the microsurgical transfer of skin, subcutaneous fat and associated vasculature from the abdomen to the chest wall. As adipose tissue is now recognized as an endocrine organ that secretes a variety of fat-specific cytokines (“adipokines”) and lipid metabolites, the possible influence of transferred abdominal fat on breast cancer progression and recurrence is emerging as an important clinical question. While it is known that fat tissue displays differential adipokine secretion depending on anatomic location, little is known about subcutaneous abdominal versus breast fat characteristics. To begin to examine this, we hypothesized that breast fat from a cancer patient would exhibit increased metabolic activity and secrete more oncogenic adipokines when compared to subcutaneous abdominal fat. Our aims were to: 1) determine the metabolic and adipokine characteristics of abdominal versus endogenous breast fat depots in breast cancer patients undergoing reconstruction and 2) examine the impact of chest wall neovascularization on abdominal fat characteristics examined in Aim 1.
Methods: Under an IRB-approved protocol, breast and subcutaneous abdominal fat were collected from 10 women undergoing mastectomy/reconstruction. Insulin signaling was measured in vitro using quantitative anti-phospho-Akt immunoblotting of adipose tissue protein lysates. In parallel, conditioned media was made by culturing minced fat from each depot in serum-free media for 8 hours, after which the media was applied to breast cancer cell lines and cell proliferation measured over time.
Results: Mean subject age was 60.7 (range 47–73) and mean BMI was 30.5 (range 25.9–36.7). Mean hemoglobin A1c was 5.6% (range 5.0–5.9%). Initial results suggest that breast fat demonstrated increased insulin sensitivity compared with abdominal fat. Conditioned media from both depots caused proliferation in MCF-10A (breast epithelial cell line) and MDA-MB-231 (triple-negative breast cancer cell line).
Conclusion: Initial data suggest that breast fat is more metabolically active than abdominal fat. Conditioned media studies indicate pro-proliferative factors are released from both depots. The conditioned media will also be analyzed for depot-specific adipokine signatures using antibody arrays. Three to six months following reconstruction, biopsies of the transferred subcutaneous abdominal fat will be done to determine if chest wall neovascularization alters insulin sensitivity and secretion of pro-proliferative factors compared to baseline abdominal tissue. Based on these studies, future studies comparing the vascularized transfer of alternative adipose depots (e.g. gluteal) could help identify the safest source of adipose tissue for post-mastectomy reconstruction.